DESCRIPTION (adapted from the application) It is well accepted that intestinal epithelial cells (IEC) play a very active role in the regulation of the immune response in the intestine. They present antigens directly to B and T cells, transport secretory IgA into the lumen, produce chemokines and cytokines, and relay signals received as neuroendocrine hormones. It would appear that a healthy epithelium is an absolute requirement for homeostasis of the digestive immune system and that a [sic] immunologic imbalance will disturb the immune response with the development of inflammatory disease. Intimately involved in the maintenance of this mucosal integrity is the intestinal intraepithelial lymphocyte (iIEL), a unique population of T lymphocytes which reside among the basolateral surface of the IECs. It seems that a delicate and complex and complex mechanism of cellular cross-talk exists between IEC and lymphocytes which maintains this equilibrium. The molecular details, however, of this complex control mechanism are largely unknown. The research in this proposal is aimed at addressing the communication between IECs and iIELs, which is certainly mediated through receptor-ligand protein pairs. To that end we have applied the phage display technique. Since in this system the genetic information is physically bound to the expression protein, enrichment of clones positive for protein-protein interactions can be obtained through repeated panning steps. We have identified portions of several, mostly novel, genes that are expressed in IECs which when expressed on the phage surface mediate binding of the phage particles to iIELs. The proposed studies are aimed at characterizing the functions of these proteins in IEC-iIEL interactions. Specifically we propose: 1-To clone the entire sequence for the proteins partially present in three phage clones. 2- To characterize the binding of iIELs of the proteins coded in these phage clones. 3- To study the effect of the binding of these three proteins on cytotoxicity, proliferation and attachment of iIELs to IECs. 4- To clone and characterize the receptors for these proteins present on the surface of iIELs.